The exosomes in tumor immunity

Liu, Yanfang; Gu, Yan; Cao, Xuetao

doi:10.1080/2162402x.2015.1027472

Cited by 177 publications

(161 citation statements)

References 93 publications

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“…2,4 Several studies describe the involvement of exosomes in the modulation of both innate and adaptive immune response through different mechanisms. 1,3,46 As for NK cells, the immunomodulatory role of exosomes appears to be multi-faceted and dependent on the identity of both the exosomes-associated cargo end exosome releasing cells. 23,47 In this context, the inhibitory action of Tex on NK cell functions has been mostly attributed to TGF-b and/or NKG2D ligands associated to these vesicles.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 In this context, a fast developing field is that focusing on how exosomes released by cancer cells in the tumor microenvironment are uptaken by different immune cell types, thereby modulating antitumor immune response and affecting tumor progression. 3,4 Natural killer (NK) cells are innate immune effectors that play a pivotal role in tumor immunosurveillance by exerting direct cytotoxic effects as well as producing a variety of cytokines. NK cell activation is tightly regulated by a fine balance between activating and inhibitory signals.…”

Section: Introductionmentioning

confidence: 99%

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Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis

et al. 2017

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Exosomes are a class of nanovesicles formed and released through the late endosomal compartment and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Here, we investigated whether genotoxic stress could promote the release of exosomes from multiple myeloma (MM) cells and studied the immunomodulatory properties they exert on NK cells, a major component of the antitumor immune response playing a key role in the immunosurveillance of MM. Our findings show that melphalan, a genotoxic agent used in MM therapy, significantly induces an increased exosome release from MM cells. MM cell-derived exosomes are capable of stimulating IFNg production, but not the cytotoxic activity of NK cells through a mechanism based on the activation of NF-kB pathway in a TLR2/ HSP70-dependent manner. Interestingly, HSP70C exosomes are primarily found in the bone marrow (BM) of MM patients suggesting that they might have a crucial immunomodulatory action in the tumor microenvironment. We also provide evidence that the CD56 high NK cell subset is more responsive to exosome-induced IFNg production mediated by TLR2 engagement. All together, these findings suggest a novel mechanism of synergism between chemotherapy and antitumor innate immune responses based on the drug-promotion of nanovesicles exposing DAMPs for innate receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis

et al. 2017

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“…40) The impact of secreted exosomes on the immune system and on tumor progression has been a controversial issue. Exosomes can mediate either immunosuppression or immune system activation depending on their cellular origin.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin Expands <i>in Vivo</i> Secretion of Circulating Exosome in Mice

Emam

Ando

Lila

et al. 2018

Biological & Pharmaceutical Bulletin

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Modulation of tumor immunity is a known factor in the antitumor activity of many chemotherapeutic agents. Exosomes are extracellular nanometric vesicles that are released by almost all types of cells, which includes cancer cells. These vesicles play a crucial role in tumor immunity. Many in vitro studies have reproduced the aggressive secretion of exosomes following treatment with conventional anticancer drugs. Nevertheless, how chemotherapeutic agents including nanomedicines such as Doxil ® affect the in vivo secretion of exosomes is yet to be elucidated. In this study, the effect of intravenous injection of either free doxorubicin (DXR) or liposomal DXR formulation (Doxil ® ) on exosome secretion was evaluated in BALB/c mice. Exosomes were isolated from serum by using an ExoQuick kit. Free DXR treatment markedly increased serum exosome levels in a post-injection time-dependent manner, while Doxil ® treatment did not. Exosomal size distribution and marker protein expressions (CD9, CD63, and TSG101) were studied. The physical/biological characteristics of treatment-induced exosomes were comparable to those of control mice. Interestingly, splenectomy significantly suppressed the copious exosomal secretions induced by free DXR. Collectively, our results indicate that conventional anticancer agents induce the secretion of circulating exosomes, presumably via stimulating immune cells of the spleen. As far as we know, this study represents the first report indicating that conventional chemotherapeutics may induce exosome secretion which might, in turn, contribute partly to the antitumor effect of chemotherapeutic agents.

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“…Johnstone et al discovered the small vesicles of endosomal origin that are released during reticulocyte differentiation and named "exosomes" (9). At present, exosomes are defined according to certain characteristic criteria, including a size between 30 and 100 nm (10,11), a density of 1.13 -1.19 g/mL (6,12), specific morphological features (i.e., a cup-or dishshaped morphology when observed with transmission electron microscopy (6), or a round shape when observed with cryo-electron microscopy (8,11), and having general characteristic protein components (CD63 and TGS101).…”

Section: Exosomesmentioning

confidence: 99%

Exosome: An Emerging Participant in the Development of Liver Disease

Guo

Wang

et al. 2017

Hepat Mon

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Context: An exosome is a type of extracellular vesicle with a diameter of 30 -100 nm and a density of 1.13 -1.19 g/m. Exosomes exist in almost all body fluids and can be secreted and absorbed by most cells. They deliver information and molecules that participate in intracellular communication, thus contributing to the progression of various diseases, such as liver diseases. Evidence Acquisition: In this study we collected and summarized the most important and new data available on the role of exosome in liver diseases by the PubMed search. The study data were collected through searching the related keywords then classified and summarized. Results: In this review, we summarize the research findings regarding the roles of exosomes in liver physiology and pathology, mainly focusing on liver diseases such as viral hepatitis, liver cancer (mostly hepatocellular carcinoma [HCC]), and liver injury caused by other pathogenic factors (alcohol, drugs, hepatotoxins, high-fat diets, parasites, etc.). Conclusions: These studies revealed the involvement of exosomes in various aspects of liver physiology and pathology and in the progress of liver diseases. More importantly, it offers a promising new direction for disease diagnosis and treatment.

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The exosomes in tumor immunity

Cited by 177 publications

References 93 publications

Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis

Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis

Doxorubicin Expands <i>in Vivo</i> Secretion of Circulating Exosome in Mice

Exosome: An Emerging Participant in the Development of Liver Disease

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